Fertility Switch Points to New Treatments

Scientists have discovered an enzyme that acts as a "fertility switch" and say their findings could help treat infertility and miscarriage and may also lead to new contraceptives.

A study in the journal Nature Medicine Sunday reports that researchers at Imperial College London found high levels of a protein called SGK1 are linked with infertility, while low levels of it make a woman more likely to have a miscarriage.

Enzymes are proteins that catalyze, or increase the rates of, chemical reactions.

Jan Brosens, who led the study at Imperial and is now at Warwick University, said its results suggested new fertility and miscarriage treatments could be designed around SGK1.

"I can envisage that in the future, we might treat the womb lining by flushing it with drugs that block SGK1 before women undergo IVF (in vitro fertilization)," he said in a statement.

"Another potential application is that increasing SGK1 levels might be used as a new method of contraception."

Infertility is a worldwide problem that experts estimate to affect between 9 and 15 percent of people of child-bearing age. More than half of those affected will seek medical advice in the hope of eventually being able to become a parent.

Around one in 100 women trying to conceive have recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

In this study, Brosens' team looked at tissue samples from the womb lining, donated by 106 women who were being treated either for unexplained infertility or recurrent miscarriage.

Those with unexplained infertility had been trying to get pregnant for two years or more, and the most common reasons for infertility had been ruled out.

The researchers found that the womb lining in these women had high levels of the enzyme SGK1, while the women suffering recurrent miscarriage had low levels of SGK1.

In further experiments using mice, the team found that levels of SGK1 in the womb lining decline during the fertile window in mice.

When the researchers implanted extra copies of an SGK1 gene into the womb lining, the mice were unable to get pregnant. This suggests a fall in SGK1 levels is essential for making the uterus receptive to embryos, they said.

The researchers said any future infertility treatment that blocks SGK1 would need to have a short-term effect, since low SGK1 levels after conception seem to be linked to miscarriage.

"Low levels of SGK1 make the womb lining vulnerable to cellular stress, which might explain why low SGK1 was more common in women who have had recurrent miscarriage," said Madhuri Salker of Imperial college, who also worked on the study.

"In the future, we might take biopsies of the womb lining to identify abnormalities that might give them a higher risk of pregnancy complications, so that we can start treating them before they get pregnant."